Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth

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Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth

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dc.contributor.author Nemeth, Zsuzsanna en_US
dc.contributor.author Csizmadia, Eva en_US
dc.contributor.author Vikstrom, Lisa en_US
dc.contributor.author Li, Mailin en_US
dc.contributor.author Bisht, Kavita en_US
dc.contributor.author Feizi, Alborz en_US
dc.contributor.author Otterbein, Sherrie en_US
dc.contributor.author Zuckerbraun, Brian en_US
dc.contributor.author Costa, Daniel B. en_US
dc.contributor.author Pandolfi, Pier Paolo en_US
dc.contributor.author Fillinger, Janos en_US
dc.contributor.author Döme, Balazs en_US
dc.contributor.author Otterbein, Leo E. en_US
dc.contributor.author Wegiel, Barbara en_US
dc.date.accessioned 2016-11-18T20:05:26Z
dc.date.issued 2016 en_US
dc.identifier.citation Nemeth, Z., E. Csizmadia, L. Vikstrom, M. Li, K. Bisht, A. Feizi, S. Otterbein, et al. 2016. “Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth.” Oncotarget 7 (17): 23919-23932. doi:10.18632/oncotarget.8081. http://dx.doi.org/10.18632/oncotarget.8081. en
dc.identifier.issn 1949-2553 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407642
dc.description.abstract We hypothesized that tumor-associated macrophages (TAMs) are controlled by the diffusible gas carbon monoxide (CO). We demonstrate that induction of apoptosis in lung tumors treated with low doses of CO is associated with increased CD86 expression and activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (Erk) 1/2 pathway in tumor microenvironment. Presence of CD86-positive cells was required for the anti-tumoral effects of CO in established A549 xenografts. We show that the effects of CO on tumor stroma and reprogramming of macrophages towards the anti-tumoral phenotype is mediated by reactive oxygen species (ROS)-dependent activation of MAPK/Erk1/2-c-myc pathway as well as Notch 1-dependent negative feedback on the metabolic enzyme heme oxygenase-1 (HO-1). We find a similar negative correlation between HO-1 and active MAPK-Erk1/2 levels in human lung cancer specimens. In summary, we describe novel non-cell autonomous mechanisms by which the diffusible gas CO dictates changes in the tumor microenvironment through the modulation of macrophages. en
dc.language.iso en_US en
dc.publisher Impact Journals LLC en
dc.relation.isversionof doi:10.18632/oncotarget.8081 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029674/pdf/ en
dash.license LAA en_US
dc.subject tumor microenvironment en
dc.subject carbon monoxide en
dc.subject macrophages en
dc.subject immunotherapy en
dc.title Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Oncotarget en
dash.depositing.author Costa, Daniel B. en_US
dc.date.available 2016-11-18T20:05:26Z

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